Excretion of tryptophan metabolites by patients with rheumatoid arthritis

Abstract

The urinary excretion of tryptophan metabolites was measured in control subjects, in patients with active rheumatoid arthritis, and in patients with related disorders. After tryptophan loading, 12/15 female patients and 4/5 male patients with active rheumatoid arthritis and a positive latex test had significantly elevated levels of one or more of the tryptophan metabolites measured. Hydroxykynurenine and kynurenine were the metabolites most frequently elevated. Although excretion of 4-pyridoxic acid was in the normal range in these subjects, administration of supplements of pyridoxine restored tryptophan metabolism toward normal in a group of 11 female patients in which this was studied. The data suggests that a high percentage of these patients have a functional pyridoxine deficiency demonstrable in tryptophan metabolism only by means of a tryptophan loading test.Le excretion urinari de metabolitos de tryptophano esseva mesurate in subjectos de controlo, in patientes con active arthritis rheumatoidee, e in patientes con relationate disordines. Post cargation con tryptophano, 12 inter 15 patientes feminin e 4 inter 5 patientes mascule con active arthritis rheumatoidee e positivitate del test a latex monstrava significative elevationes de un o plures del metabolitos de tryptophano mesurate. Hydroxycynurenina e cynurenina esseva le metabolitos elevate le plus frequentemente. Ben que le excretion de acido 4-pyridoxic esseva in iste subjectos intra le limites del norma, le administration de supplementos de pyridoxina restaurava le metabolismo de tryptophano in le direction de valores normal in un gruppo de 11 patientes feminin in qui iste aspect0 del question esseva studiate. Le datos suggere que un alte procentage de iste patientes ha un carentia functional de pyridoxina que es demonstrabile in le metabolismo de tryptophano solmente per medio de un test a cargation de tryptophano.TUDIES IN THIS LABORATORY have been concerned with the trypto-S phan metabolism of patients with certain chronic diseases. Previous studies from this laboratory have shown that several of the tryptophan metabolites shown in figure 1 were excreted in the urine in elevated amounts by patients with bladder cancer,lX2 scleroderma and acrosclerosis,3 p~r p h y r i a ,~ lupus erythmatosus5 and pregnancy.B Patients with psoriasis, atopic dermatitis, hyperthyroidism, muscular dystrophy, Friedreich's ataxia and diabetes mellitus excreted normal levels of the metabolites m e a s~r e d .~.~ This paper presents the

Correlation of kynurenine excretion with liver tryptophan pyrrolase levels in disease and after hydrocortisone induction.

“…Patients with rheumatoid arthritis formed one-third of the group, although we did not intend to contrast subjects with this disease with others or with the normal population; our purpose was merely to investigate a group heterogeneous with respect to the amount of urinary kynurenine after a tryptophan load. Rheumatoid arthritis is one of the conditions in which increased kynurenine excretion is frequently found (18), and this is seen in some of the subjects in the present study. Table II indicates that irrespective of the diagnosis, those subjects who excrete much kynurenine also have a high tryptophan pyrrolase activity in the liver.…”

Serum kynurenine in rheumatoid arthritis

“…Most patients with rheumatoid arthritis excrete in their urine increased quantities of metabolic products of tryptophan (1)(2)(3)(4)(5)(6). The products most consistently found in abnormal quantities are kynurenine, 3-hydroxyanthranilic acid, hydroxykynurenine, and xanthurenic acid.…”

Altered Tryptophan and Neopterin Metabolism In Cancer Patients

“…certain autoimmune diseases such as rheumatoid arthritis, scleroderma, Wegner's granulomatosis and cancerburden state (5,6,7). Prior to the discovery of the IDO enzyme, it was believed that some of these tryptophan metabolism abnormalities were the result of stress or hormonal induction of liver tryptophan degradation or due to a functional deficiency of vitamin B-6 causing a block in further kynurenine metabolism (8).…”